Bony Metastases Research Articles

Post-thyroidectomy metastatic thyroid cancer

The objective of this paper is to highlight the importance of tissue biopsy for histopathological diagnosis. A report of a 46-year-old farmer with post-thyroidectomy metastatic thyroid cancer. A post-thyroidectomy patient presenting with extensive skull and lumbar spine metastasis, paraparesis, huge occipital swelling and good healed scar without tumour residue. The thyroidectomy specimen was not subjected to histopathological diagnosis. Fine needle aspiration cytology of the occipital swelling revealed metastatic follicular carcinoma. Patient was placed on thyroxine 0.5mg daily with great improvement of lower limb muscle power. These bony metastases could have been reduced if proper investigation was done. There is need for continuous medical education for all clinical medical personnel.

Prognosis Scores of Tokuhashi and Tomita for Patients With Spinal Metastases of Renal Cancer

Retrospective evaluation of the prognosis scores of Tokuhashi and Tomita for life expectancy in 37 consecutive patients with spinal metastases secondary to renal cancer who underwent surgery. The score of Tokuhashi, composed of six parameters, each rated from zero to two, has been proposed in 1990 for the prognostic assessment of patients with spinal metastases. In 2001, Tomita et al. created another prognostic score, composed of three parameters, growth behaviour of the primary tumor (slow, moderate and rapid) and the evidence of visceral and bony metastases. Thirty-seven patients, surgically treated for vertebral metastases secondary to renal cancer were studied. The scores according to Tokuhashi and Tomita were calculated for each patient. Applying the Tokuhashi Score for the estimation of life expectancy of renal cancer patients with vertebral metastases was found to provide very reliable results with a statistically high significance. The analysis according to Tomita showed no correlation between predicted and real survival. The statistical analysis did not show any significance. For surgical decisions in renal cancer patients with spinal metastases, the prognostic score of Tokuhashi appears to be much more valuable than the Tomita score.

Bone Scan and Liver Ultrasound Scan in the Preoperative Staging for Primary Breast Cancer

The aim of the present study was to investigate the value of preoperative staging in primary operable breast cancer. This retrospective study included patients presenting between May 1999 and February 2004 with operable primary breast cancer. Of the 221 patients 189 had normal and 32 suspicious or positive bone scans (BS). Of the 189 patients with normal BS 182 had normal liver ultrasound (US), whereas the remaining seven patients underwent computed tomography scan which was normal in five and two confirmed liver metastases (one with abnormal LFTs). Of the 32 patients with suspicious or positive BS 26 were false positive on further investigations and the remaining six patients were confirmed to have bony metastasis (one abnormal bone profile). BS and liver US truly altered treatment in 3% of patients. False-positive results caused delay, psychological upset, and costly investigations in 14% of cases. Preoperative staging with liver US and BS should be reserved for high-risk patients.

Zinc-alpha2-glycoprotein Expression as a Predictor of Metastatic Prostate Cancer Following Radical Prostatectomy

The risk of metastatic progression for prostate cancer patients who undergo radical prostatectomy is best estimated presently based on prostate-specific antigen (PSA) doubling time (PSADT). However, additional markers of risk are needed to identify patients who may benefit from aggressive salvage treatment. A decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate epithelium was previously shown to predict biochemical recurrence, as defined by rising levels of serum PSA after radical prostatectomy. We assessed the reliability with which AZPG1 expression could predict clinical recurrence and metastatic progression. Using immunohistochemical methods, we analyzed AZPG1 expression in malignant prostate epithelium in prostatectomy specimens from 228 prostate cancer patients. Low (i.e., absent or weak) AZGP1 expression was associated with clinical recurrence (defined as confirmed localized recurrence, metastasis, or death from prostate cancer; hazard ratio [HR] = 4.8, 95% confidence interval [CI] = 2.2 to 10.7, P<.001) and with bony metastases or death from prostate cancer (HR = 8.0, 95% CI = 2.6 to 24.3, P<.001). Among the 17 patients in the cohort in whom clinical recurrence was associated with short PSADT, absent or weak AZGP1 expression was observed in 13 patients. If these preliminary findings are validated in independent cohorts, the measurement of AZGP1 levels in radical prostatectomy specimens may permit an accurate and timely assessment of risk of metastatic progression after radical prostatectomy.

A 5-Year-Old Girl With Impaired Renal Function After Autologous Bone Marrow Transplantation

ONE MARROW TRANSPLANTATION(BMT) increasingly is used for the treatmentof patients with hematologic malignancies, somemetabolic and immunologic diseases, and de-pressed bone marrow after cancer treatment. Renalinsufficiency after BMT is common and related tomanycauses.Wepresentthecaseofagirlwhohadrenalinsufficiency4monthsafterautologousBMT.

Mixed Metastatic Lung Cancer Lesions in Bone Are Inhibited by Noggin Overexpression and Rank:Fc Administration

Lung cancer metastases to bone produce a primarily mixed osteolytic/osteoblastic lesion. The purpose of this study was to determine if blockade of both pathways would inhibit the formation these lesions in bone. Inhibition of the osteoblastic lesion with noggin and the osteolytic lesion with RANK:Fc was a successful treatment strategy to inhibit progression of mixed lung cancer lesions in bone. Approximately 9-30% of patients with lung cancer develop bone metastases, leading to significant morbidity and mortality. A549 is a non-small-cell lung cancer (NSCLC) line that produces a mixed metastatic lesion in bone. We sought to determine if blockade of key components in both osteolytic and osteoblastic pathways would result in a reduction of a NSCLC tumor progression in a murine model of bony metastasis. The study used a retroviral vector overexpressing noggin (RN), a specific inhibitor of BMP, and RANK:Fc, a chimeric protein that inhibits the RANK-RANKL interaction. A549 cells were transduced with RN before implantation in SCID mice. Cells were implanted in a subcutaneous model and tibial injection model. RANK:Fc was administered twice weekly at 15 mg/kg. There were five treatment groups: A549; A549 + RN; A549 + RANK:Fc; A549 + empty vector; and A549 + RN + RANK:Fc (n = 10/group). In SCID mice who underwent subcutaneous A549 tumor cell injection, animals treated with A549 + RN had significantly smaller subcutaneous tumor size at 8 weeks. In an intratibial model of bony metastasis, animals injected with A549 cells developed a mixed lytic/blastic lesion with cortical destruction at 8 weeks. Treatment with RANK:Fc inhibited the formation of osteoclasts, led to a smaller tumor volume in bone, and inhibited the lytic component of the mixed lesion. Animals treated with A549 + RN had a decreased number of osteoblasts in bone lesions, smaller tumor volume, and inhibition of the blastic component of the mixed lesions. Combination treatment inhibited both the lytic and blastic components of the lesion. The NSCLC cell line A549 forms a mixed osteolytic/osteoblastic lesion in vivo. Noggin overexpression inhibited the formation of the osteoblastic aspect of the lesion in bone and the tumor growth in vivo. Treatment with RANK:Fc limited the formation of the lytic aspect of the mixed lesion and also inhibited the rate of in vivo tumor growth. Inhibition of both pathways is necessary to effectively inhibit the progression of mixed metastatic lesions in bone.

Reduced incidence of bony metastasis at initial prostate cancer diagnosis: Data from CaPSURE™

Purpose Despite stage migration as a result of screening, many individuals are diagnosed each year with metastatic (M+), as opposed to localized (M0), prostate cancer. This study describes features that characterize patients with M+ compared to those diagnosed with M0 disease. Materials and Methods Patients enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE™), a national, longitudinal registry of men with prostate cancer, formed the basis of this study. The prevalence, and changes with time, of patients with M+ and M0 cancer by clinical and sociodemographic characteristics were examined. Results Of 10,113 patients diagnosed between 1990 and 2003, 266 (2.6%) had M+ disease at diagnosis. From 1990 to 1997, 4.2% of 4020 total patients had M+ versus 1.6% of 6093 total patients diagnosed between 1998 and 2003 (odds ratio 0.34; 95% confidence interval 0.24−0.48; P < 0.0001). In univariate analysis, advanced age, higher prostate-specific antigen, Gleason grade, black race, lower income, and lower educational level were associated with M+ versus M0 disease ( P < 0.01). However, in multivariate analysis, only higher serum prostate-specific antigen and higher Gleason grade, and not the sociodemographic variables, remained associated with M+ disease ( P < 0.01). Patients with M+ diagnosed between 1998 and 2003 are more likely to harbor high-grade (Gleason ≥8) primary tumors (62% vs. 45%, P = 0.02) than those diagnosed between 1990 and1997. No changes in age, race, education, insurance status, or income were observed in the early versus late era. Conclusions These findings show a reduction in the incidence of metastatic disease at initial prostate cancer diagnosis. Furthermore, biologic, rather than socioeconomic, factors are associated with this type of disease presentation.

Controversies in the Management of Adenocarcinoma of the Esophagus and Esophagogastric Junction.

In the past, adenocarcinomas were thought to occur rarely in the esophagus and to comprise a small percentage of the tumors. In recent years the incidence has risen so that they represent 25% to 35% of all esophageal tumors. Epidemiological studies have shown that the tumor is more common in men than women ( approximately 8:1) and in whites than non-whites ( approximately 7:1). The most common associated condition is Barrett's esophagus, but the evaluation is clouded by the inconsistent definition of Barrett's esophagus in the gastroenterology literature. The diagnosis of Barrett's esophagus requires the identification of metaplastic glandular epithelium with goblet cells in the esophagus. The management of adenocarcinomas of the esophagus is difficult to evaluate because the tumors are frequently included with squamous carcinomas of the esophagus or adenocarcinomas of the gastric cardia. Esophageal adenocarcinomas are associated with a high rate of local recurrence when treated with surgery or radiation alone. Their pattern of spread is different from that of gastric carcinomas in that peritoneal seeding is uncommon and liver and pulmonary parenchymal metastases are less common, whereas pleural and bony metastases are more common. This would suggest that they should be analyzed as a separate clinical entity. In the absence of prospective trials, the reported experience suggests that these patients should be considered for combined surgery and preoperative or postoperative chemotherapy and radiation. Patients who are not candidates for surgery can receive effective and durable palliation from chemosensitized radiation. There are theoretical advantages to both preoperative and postoperative therapy and the selection of treatment programs should be individualized.

Permanent 125I prostate brachytherapy outcome in patients younger than 60

14553 Background: Permanent 125I prostate brachytherapy (PB) has been shown to be an effective form of treatment for men with clinically localized prostate cancer. However, the efficacy of PB in younger men is not well established, and many urologists and oncologists have been reluctant to recommend PB to younger men, since most reported PB outcome has been based on men implanted in their late 60s and 70s. Methods: Between 1/1/98 and 6/30/01, 100 consecutive men aged 49–59 (median 56) underwent PB. All had either low- or intermediate-risk disease. PB was performed without combined external beam irradiation or post-PB androgen deprivation. The prescribed radiation dose=144–145Gy, the median implant activity=38mCi, median prostate volume=36 ml. Mean day-30 post-PB CT-based implant dosimetry values were V100=94%; V150=60%; D90=160 Gy. The primary endpoint for this analysis was the 5-year biochemical no evidence of disease rate (bNED) defined by the ASTRO consensus definition. Secondary endpoints were disease-specific survival (DSS); freedom from salvage therapy (FSRx), and overall survival (OS). Median PSA followup was 59 months (maximum 93 months). Actuarial results were calculated using the Kaplan-Meier method. Results: The 5-year bNED rate was 92%. 8 patients developed biochemical failure, and 6 went on to salvage treatment with hormonal therapy. There were 2 biopsy-proven local recurrences: one in a patient with previously diagnosed bony metastases, and one with isolated seminal vesicle recurrence (prostate biopsies negative). 3 other patients with biochemical failure had negative re-biopsies at 24, 64, and 66 months post-PB. No patient received local salvage therapy. One patient died from a second malignancy (colon CA diagnosed after PB). The 5-year DSS rate = 100%; FSRx = 93%, and OS = 99%. There were 2 Grade 3 GU complications (urethral strictures) (2%) and one Grade 4 GU complication (TURP) (1%). There were no Grade 3 or 4 GI complications. Conclusions: PB is an effective treatment modality for men younger than 60, with 5 year results comparable to those reported with prostatectomy and external beam irradiation. Given that most men who fail PB do so within 5 years of the implant, there appears to be no compelling scientific reason to advise against PB in men younger than 60 solely based on their age. No significant financial relationships to disclose.

Routine staging radiology is not needed for all breast cancer patients

10648 Background: Early stage breast carcinoma is unlikely to have undergone metastatic spread at the time of presentation. The utility of routine staging liver ultrasound (LUS) and bone scan (BS) in early stage disease is unclear. We postulate that early stage breast cancer patients do not need routine radiological staging. Methods: We studied 200 patients with a diagnosis of invasive breast carcinoma. 100 with symptomatic breast cancer (SBC) and 100 with screen detected (SD). Patients’ histology, tumour markers (CEA, CA 15.3), hormone receptor status, CXR, LUS and BS results were reviewed. Results: All patients underwent curative surgery for early stage invasive breast cancer. 3 patients had liver metastases diagnosed by LUS. Two of these patients were from the SBC and one from SD (grade ≥2, mean tumour size 2.2 cm). 4 patients had bony metastases diagnosed by BS. Three of these were from the SBC and one from SD (grade ≥2, mean tumour size 3.2 cm.). No patients with low-grade T1 tumours had signs of metastasis on BS or US. Conclusions: The incidence of metastatic disease is very low in newly diagnosed early stage breast carcinoma. Our results suggest that patients with low-grade T1 tumours do not need staging BS or US. No significant financial relationships to disclose.

Obscured Bone Metastases After Administration of Hematopoietic Factor on FDG-PET

We describe interesting imaging features on a FDG-PET scan in a patient with bony metastases from a rare tumor. The lesions were obscured by intense bone marrow activity after the administration of hematopoietic factor at the time of diagnosis. Correlative MRI, CT scan, and pathology findings have also been illustrated. Follow-up FDG-PET scan demonstrated the hypermetabolic lesions.

Latest pain management for painful bony metastases

Pain management for painful bony metastases is the most important problem for symptom relief of terminally-ill cancer patients. Pathological fractures often decrease the activity of daily life (ADL) of patients, and cause deterioration of the quality of life (QOL) and prognosis. Basically pharmacological therapies of the World Health Organization (WHO) method are essential for symptom relief from cancer pain. This article provides the latest pain managements (palliative irradiation, bisphosphonate, orthopedic surgery, percutaneous vertebroplasty and radiopharmaceutical therapy) of bony metastases, and mentions the indications and the problems of these interventions. In consideration to prognosis, the QOL and patient's needs, medical staffs have to perform multidisciplinary approach for providing suitable palliative care.

Nonseminomatous Germ Cell Tumor after Chemotherapy with Residual Mass Invading the Spine

Bony metastasis is a rare feature of metastatic nonseminomatous germ cell tumor. A 25 year-old man presented with back pain radiating down both legs, and a subsequent work-up demonstrated a right-sided testicular mass with bilateral retroperitoneal lymphadenopathy and tumor involvement of the L2 vertebra. Radical inguinal orchiectomy confirmed nonseminomatous germ cell tumor, and the patient underwent chemotherapy with a residual mass and vertebral involvement by MRI. Combined vertebral resection with spinal reconstruction and retroperitoneal lymph node dissection demonstrated residual fibrosis. While bony metastasis of nonseminomatous germ cell tumors is rare, resection with spinal reconstruction can be accomplished with acceptable morbidity.

Multiple skeletal metastases from a giant cell tumour of the distal fibula with fatal outcome

A giant cell tumour is a primary lesion of bone of intermediate severity. Its histogenesis is unclear. In a few cases pulmonary metastases have been described. Multiple skeletal metastases in the absence of sarcomatous change have been observed. We present a case report of a 25-year-old woman with a recurrent giant cell tumour of the distal fibula. After a second recurrence and six years after the initial diagnosis, she rapidly developed multiple bony metastases. The outcome was fatal.

Skin-sparing mastectomy and immediate breast reconstruction: patient satisfaction and clinical outcome

Skin-sparing mastectomy (SSM) followed by immediate reconstruction has been advocated as an effective treatment option for patients with early-stage breast carcinoma. It minimizes deformity and improves cosmesis through preservation of the natural skin envelope of the breast. The purpose of this study was to evaluate postoperative morbidity, patients' satisfaction, and oncological safety for SSM and immediate breast reconstruction (IBR) with a latissimus dorsi (LD) myocutaneous flap and/or breast prosthesis in patients with operable breast cancer. Twenty-one consecutive patients with operable breast cancer undergoing 25 SSM and immediate reconstruction with an LD flap plus implant (n = 14) or implant alone (n = 11) were retrospectively studied (from 2001 through 2005). The median patients' age was 44 years (range, 30-68). Patient satisfaction with the outcome of surgery was assessed using a detailed questionnaire including a linear visual analogue scale ranging from 0 (not satisfied) to 10 (most satisfied). Eight of 20 (40%) patients required adjuvant chemotherapy, and only 2 patients required post-mastectomy radiation. Reconstruction of the nipple-areola complex was performed in 7 patients (33%) using the trefoil local flap technique. Contralateral procedures to achieve symmetry were performed in 6 (28%) patients (5 augmentations and 1 reduction mammoplasty). Histological analysis showed pure ductal carcinoma in situ (DCIS) in 4 patients and invasive carcinoma (+/- DCIS) in 20 cases, of which 5 (25%) were node positive. One prophylactic mastectomy in a BRCA-2 carrier was negative for malignancy. Tumor size ranged from 5 to 90 mm. The surgical margins were clear in all cases. There was no delay in time to commencement of adjuvant therapies. After a mean follow-up period of 13.5 months (range, 5-46 months), none of the patients developed locoregional recurrence. Only 1 patient (5%) developed systemic recurrence (bony metastases). Overall survival was 100%. The incidence of flap necrosis/loss, implant loss, wound infection, or hematoma requiring surgical evacuation was 0%, 0%, 0%, and 0%, respectively. Capsule formation requiring capsulotomy was observed in 3 of 21 patients (14%). The median patient satisfaction score was 10 (range, 6-10). SSM and IBR for operable breast cancer is associated with a high level of patient satisfaction and low morbidity. The procedure seems to be oncologically safe, even in patients with high-risk (T3 or node-positive) carcinoma. The latter needs to be confirmed with greater numbers of patients and longer follow-up.

Bisphosphonatassoziierte Osteonekrose des Kiefers

Bisphosphonates (BP) are widely used in patients with osteoporosis or malignant tumors with bony metastases such as breast cancer and plasmocytoma because of their potency to affect osteoclasts and bone resorption. Osteonecrosis of the jaw (ONJ) has been described as a potential side effect since 2003. After a review of the literature we present results of a questionnaire, which was sent to departments of oral and maxillofacial surgery (OMFS) in German-speaking countries. We present 349 patients from the literature, 54 patients from the departments of OMFS and 19 cases from our own department. These patients ware analyzed depending on their disease, their medication, localization of the affected area, histological signs and therapeutic outcome. Of 73 patients, 68 (93%) were treated with pamidronate or zoledronate; 69 (94%) patients suffered from malignant diseases, 3 (5%) had osteoporosis, and 1 (1%) had Paget's disease. In 57 (78%) patients the ONJ affected the mandible, in 12 (16%) the maxilla and in 4 (5%) both jaws. A previous tooth extraction was reported in 38 (52%) patients, and in 35 (48%) ONJ occurred spontaneously. Histological findings were similar to osteomyelitis with a high number of actinomyces colonies. Nine (12%) patients received non-surgical treatment only, 52 (71%) patients underwent minor surgical procedures (e. g. decortication) and 19 (26%) patients underwent marginal or segmental resection of the jaw. Considering all treatment modalities, healing was achieved in 55; the most effective was marginal and segmental resection (88%). Though millions of patients receive BP treatment only a few suffer from ONJ. The incidence in cancer patients with pamidronate and zoledronate therapy is 4%-10%. Because of the similarity to "phossy jaw", seen in patients dealing with white phosphorus in the nineteenth century, some authors call the new entity "bis-phossy jaw". As the pathogenesis of ONJ is not clear we recommend that the descriptive term bisphosphonate-associated osteonecrosis should be used. Bone resection and safe soft tissue closure is the treatment of choice. We recommend systematic dental care for patients receiving BP medication. Information exchange between oncologists, oral and maxillofacial surgeons and dentists is important.

A Case Report: Breast Cancer Metastasis and Implications of Bony Metastasis on Activity and Ambulation

Patients with chronic rheumatological conditions are often referred to physical therapists for management of related impairments. If a patient's medical history includes cancer, a consideration for metastatic disease must be made during the physical therapy (PT) exam process. Failure to do so may result in ineffective or even contraindicated PT. This report describes a 56 y/o female teacher with a history of advanced breast cancer, referred to PT for shoulder pain, limited range of motion (ROM), and work limitations. On exam, the PT was suspicious of metastatic breast cancer and referred the patient for further testing. Imaging studies confirmed bony metastasis and radiation treatment was started. A PT program was then instituted for palliation. A thorough assessment of the patient's cancer history, relative risk of recurrence, and the presence of metastatic disease is essential. The PT differential diagnosis raised concerns about the patient's cancer disease state because the PT had an understanding of the implications of the cancer history and presenting signs and symptoms associated with a presentation of bone metastases.

Solitary Bony Metastasis From Renal Cell Carcinoma: Significance of Surgical Treatment

Solitary Bony Metastasis From Renal Cell Carcinoma: Significance of Surgical Treatment

Extra-salivary gland presentations of adenoid cystic carcinoma: A report of three cases

Adenoid cystic carcinoma (ACC) is a malignant neoplasm most commonly originating in salivary glands of the head and neck area. When ACC presents outside of these locations, the diagnosis may become more challenging. We describe three cases of ACC presenting in extra-salivary gland sites. Two cases were metastatic; in case 1 the initial presentation was widespread bony metastasis of unknown primary origin. The other metastatic case (case 2) was from a patient presenting with a pleural effusion and a history of previously treated metastatic pulmonary ACC. The pleural effusion cytology was unusual in that exfoliated ACC cells were present in the effusion itself, a rare occurrence. Case 3 was a primary bronchial ACC. In conclusion, ACC can present in various body sites and cytologists must consider this neoplasm when presented with a basaloid carcinoma of uncertain origin.

Bone scanning: its lack of value in the follow-up of patients with breast cancer.

Three hundred and fifty-four women with primary operable breast cancer had a bone scan performed within 6 weeks of a simple mastectomy. Eight (2.3 per cent) were positive, but 7 of these patients had radiological evidence of bony metastases. Follow-up bone scans 1 year postoperatively on 278 patients showed only 12 (4.3 per cent) positive, and of these, 9 had other radiological evidence of metastatic disease. At 2 years postoperatively there were 13 (9.2 per cent) positive bone scans amongst 141 patients. Only 2 of these 13 had no other evidence of metastases. Although a bone scan is a useful investigation in patients with bone pain, there is no place for routine bone scanning in either the staging or follow-up of women with operable breast cancer.